The renin-angiotensin system (RAAS) is a major physiological regulator of body fluid volume, electrolyte balance, and arterial pressure. Majority of the biological actions of angiotensin II (Ang II), the principal effector peptide of the RAAS, are attributed to its action at the Ang II subtype-1 receptor (AT1R). Ang II also stimulates its subtype-2 receptor (AT2R) to mainly produce vasodilation and inhibition of cell hypertrophy and proliferation. However, the functions of the AT2R are not completely unknown. Recently, a new receptor that binds to renin/prorenin receptor was discovered and termed renin/prorenin receptor (RR). The role of the RR in physiology and pathology is unknown. Preliminary data from our laboratory' and others suggested that RR mediates specific effects independent of Ang II. Stimulation of RR seems to induce rapid activation of mitogen-activated protein kinases p44/p42. Currently, the exact distribution, regulation and functions of the RRs in the kidney are unknown. Preliminary data presented in this application suggest that renin receptor is present in the renal glomeruli and tubules and is regulated by salt intake. In addition, there are preliminary data to suggest an interaction between, AT1R or AT2R and the RR. This proposal will expand on these preliminary studies and will address the following questions: 1) What are the factors that regulate the expression of the RR? 2) What are the consequences (functions) resulting from RR stimulation? 3) Is there a cross talk between the AT1R or the AT2R and RR? 4) What is the role of RR in renovascular hypertension? The main hypothesis of this proposal is that: The renal RR contributes to development of renal inflammation and fibrosis. The specific aims for this proposal are: AIM 1: To test the hypothesis that sodium intake regulates RR expression and activity. AIM II: To test the hypothesis that AT1R or AT2R regulate RR expression and activity. AIM III: To test the hypothesis that RR expression and activity is increased in renovascular hypertension rat model. Information gained from this proposal will lead to increased understanding of the pathophysiology of hypertension and development of novel therapies for its management. [unreadable] [unreadable] [unreadable]